This grant will be done primarily in Argentina at the Department of Physiology, School of Medicine, University of Buenos Aires in collaboration with Valeria Della-Maggiore, as an extension of NIH Grant No. P01 NS044393. Our daily routine involves acting on objects in our vicinity to achieve different goals. Sudden, unpredictable modifications in the environment require immediate adjustment of these well-practiced movements by updating the initial motor plan online, while persistent perturbations can be adapted to through learning over a longer time scale. Both types of adjustments may partly rely on the nervous system's ability to predict the future state of the motor system. An intriguing possibility is that the same mechanism necessary to adjust skilled behavior may be used at a higher cognitive level to predict the outcome of actions performed by others. This phenomenon, known as action observation, may be the basis to understanding other people's actions and learning by imitation. The present research project is aimed at identifying the neural substrates of motor prediction in humans and evaluating its contribution to the production and perception of action. These issues will be approached experimentally using transcranial magnetic stimulation and functional magnetic resonance imaging to characterize the role and timing of dorsal premotor and posterior parietal cortices in the prediction of action during: 1) the online adjustment of movement;2) visuomotor learning;3) observation of actions performed by others. PUBLIC HEALTH RELEVANCE: A better understanding of the role of posterior parietal and dorsal premotor cortices during production and perception of action will be informative at many levels. It may provide clues to the mechanism by which children learn social cues from observing and predicting the actions of others and how or why such learning goes awry in disorders such as autism or schizophrenia. It is also relevant for understanding the deficits of patients with neurological damage affecting the processing of visuomotor transformations such as optic ataxia (deficit in accurately reaching to objects) and ideomotor apraxia (deficit in imitating gestures under command) and, thus, may guide the development of the appropriate therapy to treat these patients. Finally, due to their role in movement preparation and movement intention, the PMd and PPC appear as suitable brain regions for the control of human prosthetics. These devices are aimed at aiding paralyzed patients interact with their environment. Neurophysiological activity of the PPC or PMd, could be decoded into signals to activate stimulators imbedded in the muscles of a patient, initiate the movement of a prosthetic arm or operate external devices such as a computer (Andersen et al., 2004;Musallam et al., 2004,Bokil et. al., 2006). Knowing the time course of PPC and PMd processing may help guide the interpretation of neuronal signals during the redirection of movement intention, and train adaptive algorithms to predict the goal and consequences of other people's actions solely based on neuronal activity elicited during action rehearsal.